Folic Acid in Stroke Prevention in Countries without Mandatory Folic Acid Food Fortification: A Meta-Analysis of Randomized Controlled Trials
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Background and Purpose Additional folic acid (FA) treatment appears to have a neutral effect on reducing vascular risk in countries that mandate FA fortification of food (e.g., USA and Canada). However, it is uncertain whether FA therapy reduces stroke risk in countries without FA food fortification. The purpose of this study was to comprehensively evaluate the efficacy of FA therapy on stroke prevention in countries without FA food fortification. Methods PubMed, EMBASE, and clinicaltrials.gov from January 1966 to August 2016 were searched to identify relevant studies. Relative risk (RR) with 95% confidence interval (CI) was used as a measure of the association between FA supplementation and risk of stroke, after pooling data across trials in a random-effects model. Results The search identified 13 randomized controlled trials (RCTs) involving treatment with FA that had enrolled 65,812 participants, all of which stroke was reported as an outcome measure. After all 13 RCTs were pooled, FA therapy versus control was associated with a lower risk of any future stroke (RR, 0.85; 95% CI, 0.77 to 0.95). FA alone or combination of FA and minimal cyanocobalamin (≤0.05 mg/day) was associated with a lower risk of future stroke (RR, 0.75; 95% CI, 0.66 to 0.86) whereas combination of FA and cyanocobalamin (≥0.4 mg/day) was not associated with a lower risk of future stroke (RR, 0.95; 95% CI, 0.86 to 1.05). Conclusions FA supplement reduced stroke in countries without mandatory FA food fortification. The benefit was found mostly in patients receiving FA alone or combination of FA and minimal cyanocobalamin.
Abstract
Background and Purpose Additional folic acid (FA) treatment appears to have a neutral effect on reducing vascular risk in countries that mandate FA fortification of food (e.g., USA and Canada). However, it is uncertain whether FA therapy reduces stroke risk in countries without FA food fortification. The purpose of this study was to comprehensively evaluate the efficacy of FA therapy on stroke prevention in countries without FA food fortification. Methods PubMed, EMBASE, and clinicaltrials.gov from January 1966 to August 2016 were searched to identify relevant studies. Relative risk (RR) with 95% confidence interval (CI) was used as a measure of the association between FA supplementation and risk of stroke, after pooling data across trials in a random-effects model. Results The search identified 13 randomized controlled trials (RCTs) involving treatment with FA that had enrolled 65,812 participants, all of which stroke was reported as an outcome measure. After all 13 RCTs were pooled, FA therapy versus control was associated with a lower risk of any future stroke (RR, 0.85; 95% CI, 0.77 to 0.95). FA alone or combination of FA and minimal cyanocobalamin (≤0.05 mg/day) was associated with a lower risk of future stroke (RR, 0.75; 95% CI, 0.66 to 0.86) whereas combination of FA and cyanocobalamin (≥0.4 mg/day) was not associated with a lower risk of future stroke (RR, 0.95; 95% CI, 0.86 to 1.05). Conclusions FA supplement reduced stroke in countries without mandatory FA food fortification. The benefit was found mostly in patients receiving FA alone or combination of FA and minimal cyanocobalamin.
참고문헌 (58)
- Homocysteine Studies Collaboration, "Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis", JAMA, 288, pp.2015~2022 (2002)[DOI]
- Stanger O, "Clinical use and rational management of homocysteine, folic acid, and B vitamins in cardiovascular and thrombotic diseases", Z Kardiol, 93, pp.439~453 (2004)
- Homocysteine Lowering Trialists' Collaboration, "Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials", Am J Clin Nutr, 82, pp.806~812 (2005)[DOI]
- Marti-Carvajal AJ, "Homocysteine-lowering interventions for preventing cardiovascular events", Cochrane Database Syst Rev, 1 (2015)
- Li Y, "Folic acid supplementation and the risk of cardiovascular diseases: a meta-analysis of randomized controlled trials", J Am Heart Assoc, 5, pp.e003768~ (2016)[DOI]
- Lee M, "Efficacy of homocysteine-lowering therapy with folic acid in stroke prevention: a meta-analysis", Stroke, 41, pp.1205~1212 (2010)[DOI]
- Huo Y, "Efficacy of folic acid supplementation in stroke prevention: new insight from a meta-analysis", Int J Clin Pract, 66, pp.544~551 (2012)[DOI]
- Ji Y, "Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease: a meta-analysis", Neurology, 81, pp.1298~1307 (2013)[DOI]
- Yang Q, "Improvement in stroke mortality in Canada and the United States, 1990 to 2002", Circulation, 113, pp.1335~1343 (2006)[DOI]
- Huo Y, "Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial", JAMA, 313, pp.1325~1335 (2015)[DOI]
- Kotwal J, "Effectiveness of homocysteine lowering vitamins in prevention of thrombotic tendency at high altitude area: a randomized field trial", Thromb Res, 136, pp.758~762 (2015)[DOI]
- Moher D, "Preferred reporting items for systematic reviews and metaanalyses: the PRISMA statement", BMJ, 339, pp.b2535~ (2009)[DOI]
- Higgins J, "Cochrane Handbook for Systematic Reviews of Interventions" (2008), The Cochrane Collaboration
- Sterne JA, "Funnel plots for detecting bias in metaanalysis: guidelines on choice of axis", J Clin Epidemiol, 54, pp.1046~1055 (2001)[DOI]
- Wetterslev J, "Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis", J Clin Epidemiol, 61, pp.64~75 (2008)[DOI]
- Toole JF, "Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (visp) randomized controlled trial", JAMA, 291, pp.565~575 (2004)[DOI]
- Wrone EM, "Randomized trial of folic acid for prevention of cardiovascular events in end-stage renal disease", J Am Soc Nephrol, 15, pp.420~426 (2004)[DOI]
- Lonn E, "Homocysteine lowering with folic acid and B vitamins in vascular disease", N Engl J Med, 354, pp.1567~1577 (2006)[DOI]
- Cole BF, "Folic acid for the prevention of colorectal adenomas: a randomized clinical trial", JAMA, 297, pp.2351~2359 (2007)[DOI]
- Jamison RL, "Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial", JAMA, 298, pp.1163~1170 (2007)[DOI]
- Albert CM, "Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial", JAMA, 299, pp.2027~2036 (2008)[DOI]
- House AA, "Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial", JAMA, 303, pp.1603~1609 (2010)[DOI]
- Bostom AG, "Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the folic acid for vascular outcome reduction in transplantation trial", Circulation, 123, pp.1763~1770 (2011)[DOI]
- Lamas GA, "Oral high-dose multivitamins and minerals after myocardial infarction: a randomized trial", Ann Intern Med, 159, pp.797~805 (2013)[DOI]
- Mark SD, "Lowered risks of hypertension and cerebrovascular disease after vitamin", mineral supplementation: the Linxian Nutrition Intervention Trial, 1996, pp.143, 658~664
- Liem AH, "Efficacy of folic acid when added to statin therapy in patients with hypercholesterolemia following acute myocardial infarction: a randomised pilot trial", Int J Cardiol, 93, pp.175~179 (2004)[DOI]
- Liem A, "Secondary prevention with folic acid: results of the Goes extension study", Heart, 91, pp.1213~1214 (2005)[DOI]
- Bonaa KH, "Homocysteine lowering and cardiovascular events after acute myocardial infarction", N Engl J Med, 354, pp.1578~1588 (2006)[DOI]
- Righetti M, "Homocysteinelowering vitamin B treatment decreases cardiovascular events in hemodialysis patients", Blood Purif, 24, pp.379~386 (2006)[DOI]
- Zoungas S, "Cardiovascular morbidity and mortality in the Atherosclerosis and Folic Acid Supplementation Trial (asfast) in chronic renal failure: a multicenter, randomized, controlled trial", J Am Coll Cardiol, 47, pp.1108~1116 (2006)[DOI]
- Ebbing M, "Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial", JAMA, 300, pp.795~804 (2008)[DOI]
- Galan P, "Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial", BMJ, 341, pp.c6273~ (2010)[DOI]
- VITATOPS Trial Study Group, "B vitamins in patients with recent transient ischaemic attack or stroke in the vitamins to Prevent Stroke (vitatops) trial: a randomised, double-blind, parallel, placebo-controlled trial", Lancet Neurol, 9, pp.855~865 (2010)[DOI]
- Heinz J, "B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease: results of a randomized controlled trial", Circulation, 121, pp.1432~1438 (2010)[DOI]
- Study of the Effectiveness of Additional Reductions in Cholesterol, "Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial", JAMA, 303, pp.2486~2494 (2010)[DOI]
- Spence JD, "B-vitamin therapy for diabetic nephropathy: reply", JAMA, 304, pp.636~637 (2010)
- Spence JD, "Vitamin intervention for stroke prevention trial: an efficacy analysis", Stroke, 36, pp.2404~2409 (2005)[DOI]
- Spence JD, "B vitamins in stroke prevention: time to reconsider", Lancet Neurol, 16, pp.750~760 (2017)[DOI]
- Spence JD, "Understanding the complexity of homocysteine lowering with vitamins: the potential role of subgroup analyses", JAMA, 306, pp.2610~2611 (2011)[DOI]
- Xu X, "Efficacy of folic acid therapy on the progression of chronic kidney disease: the renal substudy of the China stroke primary prevention trial", JAMA Intern Med, 176, pp.1443~1450 (2016)[DOI]
- Robertson J, "Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products", CMAJ, 172, pp.1569~1573 (2005)[DOI]
- Spence JD, "Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke", Nutr Res, 36, pp.109~116 (2016)[DOI]
- Iso H, "Serum total homocysteine concentrations and risk of stroke and its subtypes in Japanese", Circulation, 109, pp.2766~2772 (2004)[DOI]
- Perini F, "Elevated plasma homocysteine in acute stroke was not associated with severity and outcome: stronger association with small artery disease", Neurol Sci, 26, pp.310~318 (2005)[DOI]
- Khan U, "Homocysteine and its relationship to stroke subtypes in a uk black population: the south London ethnicity and stroke study", Stroke, 39, pp.2943~2949 (2008)[DOI]
- Ma Y, "Homocysteine and ischemic stroke subtype: a relationship study in Chinese patients", Neurol Res, 32, pp.636~641 (2010)[DOI]
- Vermeer SE, "Homocysteine, silent brain infarcts, and white matter lesions: the Rotterdam Scan Study", Ann Neurol, 51, pp.285~289 (2002)[DOI]
- Seshadri S, "Association of plasma total homocysteine levels with subclinical brain injury: cerebral volumes, white matter hyperintensity, and silent brain infarcts at volumetric magnetic resonance imaging in the Framingham Offspring Study", Arch Neurol, 65, pp.642~649 (2008)
- Tseng YL, "Association of plasma homocysteine concentration with cerebral white matter hyperintensity on magnetic resonance images in stroke patients", J Neurol Sci, 284, pp.36~39 (2009)[DOI]
- Kloppenborg RP, "Homocysteine and cerebral small vessel disease in patients with symptomatic atherosclerotic disease. The SMARTMR study", Atherosclerosis, 216, pp.461~466 (2011)[DOI]
- Xu C, "Relationship between homocysteine level and diabetic retinopathy: a systematic review and meta-analysis", Diagn Pathol, 9, pp.167~ (2014)[DOI]
- Xie D, "Hyperhomocysteinemia predicts renal function decline: a prospective study in hypertensive adults", Sci Rep, 5, pp.16268~ (2015)[DOI]
- Cavalieri M, "B vitamins and magnetic resonance imaging-detected ischemic brain lesions in patients with recent transient ischemic attack or stroke: the vitamins to Prevent Stroke (VITATOPS) MRI-substudy", Stroke, 43, pp.3266~3270 (2012)[DOI]
- Vermeulen EG, "Effect of homocysteine-lowering treatment with folic acid plus vitamin B on cerebrovascular atherosclerosis and white matter abnormalities as determined by MRA and MRI: a placebo-controlled, randomized trial", Eur J Clin Invest, 34, pp.256~261 (2004)[DOI]
- Crider KS, "Folic acid food fortification-its history, effect, concerns, and future directions", Nutrients, 3, pp.370~384 (2011)[DOI]
- Jacques PF, "The effect of folic acid fortification on plasma folate and total homocysteine concentrations", N Engl J Med, 340, pp.1449~1454 (1999)[DOI]
- Tighe P, "A dose-finding trial of the effect of long-term folic acid intervention: implications for food fortification policy", Am J Clin Nutr, 93, pp.11~18 (2011)[DOI]
- Kelly PJ, "Low vitamin B6 but not homocyst(e)ine is associated with increased risk of stroke and transient ischemic attack in the era of folic acid grain fortification", Stroke, 34, pp.e51~e54 (2003)[DOI]